Multivalent inhibitors for carbohydrate-processing enzymes: beyond the "lock-and-key" concept

Chemistry. 2014 Sep 8;20(37):11616-28. doi: 10.1002/chem.201402537. Epub 2014 Jul 31.

Abstract

During the last decades, tremendous chemical efforts have been dedicated to design monovalent inhibitors of carbohydrate-processing enzymes, with comparatively few rewards in terms of marketed drugs. Recently, an alternative to the traditional "lock and key" approach has emerged. Multivalency, a widely used strategy for lectin inhibition, has been successfully applied to specific glycosidases and glycosyltransferases.

Keywords: carbohydrates; drug design; enzymes; inhibitors.

Publication types

  • Review

MeSH terms

  • Animals
  • Carbohydrate Metabolism*
  • Carbohydrates / chemistry*
  • Drug Design
  • Enzyme Inhibitors / chemistry*
  • Enzyme Inhibitors / pharmacology*
  • Glycoside Hydrolases / antagonists & inhibitors*
  • Glycoside Hydrolases / chemistry
  • Glycoside Hydrolases / metabolism
  • Humans
  • Models, Molecular
  • Neuraminidase / antagonists & inhibitors*
  • Neuraminidase / chemistry
  • Neuraminidase / metabolism
  • Structure-Activity Relationship
  • alpha-Mannosidase / antagonists & inhibitors*
  • alpha-Mannosidase / chemistry
  • alpha-Mannosidase / metabolism

Substances

  • Carbohydrates
  • Enzyme Inhibitors
  • Glycoside Hydrolases
  • Neuraminidase
  • alpha-Mannosidase